Pediatric Nephrology

, Volume 34, Issue 2, pp 187–194 | Cite as

State-of-the-art immunosuppression protocols for pediatric renal transplant recipients

  • Lars PapeEmail author
Part of the following topical collections:
  1. What’s New in Renal Transplantation


Immunosuppressive protocols used in pediatric kidney transplantation have changed substantially within the last decade. Many transplant centers now focus on the use of tacrolimus and mycophenolate mofetil in combination with early steroid withdrawal, frequently combined with antibody induction therapy. However, this approach is mainly based on treatment efficacy and—compared to other immunosuppressive regimens used in this context—leads to higher rates of viral infections in patients. In this review I assess data from prospective, interventional trials of immunosuppressive therapy in pediatric kidney transplantation. However, since there is a paucity of randomized controlled trials, I also describe the results of studies with weaker designs. The advantages and disadvantages of different immunosuppressive strategies are discussed. Within this framework I suggest ideas for individualized immunosuppressive regimens based on different stratificators that could effect a change from a ‘one size fits all’ to a tailored approach for initial and maintenance immunosuppressive therapy after renal transplantation in the pediatric setting.


Pediatric transplantation Immunosuppressive therapy Viral infections Rejections Evidence Graft survival 


Compliance with ethical standards

Conflicts of interest

Lars Pape has received speaker’s honoraria and travel grants from Novartis Pharmaceuticals and travel grants from Astellas and Sanofi Aventis.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.


  1. 1.
    Cooperative European Paediatric Renal Transplant Initiative (CERTAIN) registry. Accessed 1 July 2017
  2. 2.
    Hart A, Smith JM, Skeans MA, Gustafson SK, Stewart DE, Cherikh WS, Wainright JL, Kucheryavaya A, Woodbury M, Snyder JJ, Kasiske BL, Israni AK (2017) OPTN/SRTR 2015 annual data report: kidney. Am J Transplant 17[Suppl 1]:21–116CrossRefGoogle Scholar
  3. 3.
    Axelrod DA, Naik AS, Schnitzler MA, Segev DL, Dharnidharka VR, Brennan DC, Bae S, Chen J, Massie A, Lentine KL (2016) National variation in use of immunosuppression for kidney transplantation: a call for evidence-based regimen selection. Am J Transplant 16:2453–2462CrossRefGoogle Scholar
  4. 4.
    Nehus E, Liu C, Hooper DK, Macaluso M, Kim MO (2015) Clinical practice of steroid avoidance in pediatric kidney transplantation. Am J Transplant 15:2203–2210CrossRefGoogle Scholar
  5. 5.
    Murad MH, Asi N, Alsawas M, Alahdab F (2016) New evidence pyramid. Evid Based Med 21:125–127CrossRefGoogle Scholar
  6. 6.
    Brooks RJ, Higgins GY, Webster AC (2010) Systematic review of randomized controlled trial quality in pediatric kidney transplantation. Pediatr Nephrol 25:2383–2392CrossRefGoogle Scholar
  7. 7.
    Fine RN, Stablein D, Cohen AH, Tejani A, Kohaut E (2002) Recombinant human growth hormone post-renal transplantation in children: a randomized controlled study of the NAPRTCS. Kidney Int 62:688–696CrossRefGoogle Scholar
  8. 8.
    Sanchez CP, Kuizon BD, Goodman WG, Gales B, Ettenger RB, Boechat MI, Wang Y, Elashoff R, Salusky IB (2002) Growth hormone and the skeleton in pediatric renal allograft recipients. Pediatr Nephrol 17:322–328CrossRefGoogle Scholar
  9. 9.
    El-Husseini AA, El-Agroudy AE, El-Sayed MF, Sobh MA, Ghoneim MA (2004) Treatment of osteopenia and osteoporosis in renal transplant children and adolescents. Pediatr Transplant 8:357–361CrossRefGoogle Scholar
  10. 10.
    Smith JM, Wong CS, Salamonik EB, Hacker BM, McDonald RA, Mancl LA, Williams BJ, Ibrahim A, Roberts FA (2006) Sonic tooth brushing reduces gingival overgrowth in renal transplant recipients. Pediatr Nephrol 21:1753–1759CrossRefGoogle Scholar
  11. 11.
    Ferraris JR, Pasqualini T, Alonso G, Legal S, Sorroche P, Galich AM, Jasper H, Deflazacort Study Group (2007) Effects of deflazacort vs. methylprednisone: a randomized study in kidney transplant patients. Pediatr Nephrol 22:734–741CrossRefGoogle Scholar
  12. 12.
    Trompeter R, Filler G, Webb NJ, Watson AR, Milford DV, Tyden G, Grenda R, Janda J, Hughes D, Ehrich JH, Klare B, Zacchello G, Bjorn Brekke I, McGraw M, Perner F, Ghio L, Balzar E, Friman S, Gusmano R, Stolpe J (2002) Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation. Pediatr Nephrol 17:141–149CrossRefGoogle Scholar
  13. 13.
    Cransberg K, Cornelissen M, Lilien M, Van Hoeck K, Davin JC, Nauta J (2007) Maintenance immunosuppression with mycophenolate mofetil and corticosteroids in pediatric kidney transplantation: temporary benefit but not without risk. Transplantation 83:1041–1047CrossRefGoogle Scholar
  14. 14.
    Höcker B, Zencke S, Krupka K, Fichtner A, Pape L, Dello Strologo L, Guzzo I, Topaloglu R, Kranz B, König J, Bald M, Webb NJ, Noyan A, Dursun H, Marks S, Yalcinkaya F, Thiel F, Billing H, Pohl M, Fehrenbach H, Bruckner T, Tönshoff B (2016) Cytomegalovirus infection in pediatric renal transplantation and the impact of chemoprophylaxis with (Val-)Ganciclovir. Transplantation 100:862–870CrossRefGoogle Scholar
  15. 15.
    Benfield MR, Tejani A, Harmon WE, McDonald R, Stablein DM, McIntosh M, Rose S, CCTPT Study Group (2005) A randomized multicenter trial of OKT3 mAbs induction compared with intravenous cyclosporine in pediatric renal transplantation. Pediatr Transplant 9:282–292CrossRefGoogle Scholar
  16. 16.
    Offner G, Toenshoff B, Hocker B, Krauss M, Bulla M, Cochat P, Fehrenbach H, Fischer W, Foulard M, Hoppe B, Hoyer PF, Jungraithmayr TC, Klaus G, Latta K, Leichter H, Mihatsch MJ, Misselwitz J, Montoya C, Muller-Wiefel DE, Neuhaus TJ, Pape L, Querfeld U, Plank C, Schwarke D, Wygoda S, Zimmerhackl LB (2008) Efficacy and safety of basiliximab in pediatric renal transplant patients receiving cyclosporine, mycophenolate mofetil, and steroids. Transplantation 86:1241–1248CrossRefGoogle Scholar
  17. 17.
    Fleming JN, Taber DJ, Pilch NA, Srinivas TR, Chavin KD (2016) Yes, we still need IL-2 receptor antagonists. Am J Transplant 16:3308–3309CrossRefGoogle Scholar
  18. 18.
    Höcker B, Weber LT, Feneberg R, Drube J, John U, Fehrenbach H, Pohl M, Zimmering M, Fründ S, Klaus G, Wuhl E, Tönshoff B (2010) Improved growth and cardiovascular risk after late steroid withdrawal: 2-year results of a prospective, randomised trial in paediatric renal transplantation. Nephrol Dial Transplant 25:617–624CrossRefGoogle Scholar
  19. 19.
    Grenda R, Watson A, Trompeter R, Tonshoff B, Jaray J, Fitzpatrick M, Murer L, Vondrak K, Maxwell H, van Damme-Lombaerts R, Loirat C, Mor E, Cochat P, Milford DV, Brown M, Webb NJ (2010) A randomized trial to assess the impact of early steroid withdrawal on growth in pediatric renal transplantation: the TWIST study. Am J Transplant 10:828–836CrossRefGoogle Scholar
  20. 20.
    Sarwal MM, Ettenger RB, Dharnidharka V, Benfield M, Mathias R, Portale A, McDonald R, Harmon W, Kershaw D, Vehaskari VM, Kamil E, Baluarte HJ, Warady B, Tang L, Liu J, Li L, Naesens M, Sigdel T, Waskerwitz J, Salvatierra O (2012) Complete steroid avoidance is effective and safe in children with renal transplants: a multicenter randomized trial with three-year follow-up. Am J Transplant 12:2719–2729CrossRefGoogle Scholar
  21. 21.
    Haller MC, Royuela A, Nagler EV, Pascual J, Webster AC (2016) Steroid avoidance or withdrawal for kidney transplant recipients. Cochrane Database Syst Rev 22:CD005632Google Scholar
  22. 22.
    Zhang H, Zheng Y, Liu L, Fu Q, Li J, Huang Q, Liu H, Deng R, Wang C (2016) Steroid avoidance or withdrawal regimens in paediatric kidney transplantation: a meta-analysis of randomised controlled trials. PLoS One 11:e0146523CrossRefGoogle Scholar
  23. 23.
    Benfield MR, Bartosh S, Ikle D, Warshaw B, Bridges N, Morrison Y, Harmon W (2010) A randomized double-blind, placebo controlled trial of steroid withdrawal after pediatric renal transplantation. Am J Transplant 10:81–88CrossRefGoogle Scholar
  24. 24.
    Ettenger R, Tönshoff B, Tedesco H, Dello Strologo L, Marks S, Pape L, Martzloff E, Rauer B, Ng J, Lopez P (2017) Efficacy and safety of everolimus with reduced-exposure tacrolimus and corticosteroid withdrawal in de novo pediatric renal transplant recipients: 12-month results from the CRADLE study In: Abstracts of the 2017 American Transplant Congress. Abstract #569. Am J Transplant 17[Suppl 3]:100Google Scholar
  25. 25.
    Ahlenstiel-Grunow T, Koch A, Grosshennig A, Fromke C, Sester M, Sester U, Schroder C, Pape L (2014) A multicenter, randomized, open-labeled study to steer immunosuppressive and antiviral therapy by measurement of virus (CMV, ADV, HSV)-specific T cells in addition to determination of trough levels of immunosuppressants in pediatric kidney allograft recipients (IVIST01-trial): study protocol for a randomized controlled trial. Trials 15:324CrossRefGoogle Scholar
  26. 26.
    Staskewitz A, Kirste G, Tonshoff B, Weber LT, Boswald M, Burghard R, Helmchen U, Brandis M, Zimmerhackl LB (2001) Mycophenolate mofetil in pediatric renal transplantation without induction therapy: results after 12 months of treatment. German Pediatric Renal Transplantation study Group. Transplantation 71:638–644CrossRefGoogle Scholar
  27. 27.
    Henne T, Latta K, Strehlau J, Pape L, Ehrich JH, Offner G (2003) Mycophenolate mofetil-induced reversal of glomerular filtration loss in children with chronic allograft nephropathy. Transplantation 76:1326–1330CrossRefGoogle Scholar
  28. 28.
    Brunkhorst LC, Fichtner A, Hocker B, Burmeister G, Ahlenstiel-Grunow T, Krupka K, Bald M, Zapf A, Tonshoff B, Pape L (2015) Efficacy and safety of an everolimus- vs. a mycophenolate mofetil-based regimen in pediatric renal transplant recipients. PLoS One 10:e0135439CrossRefGoogle Scholar
  29. 29.
    Smith JM, Martz K, Blydt-Hansen TB (2013) Pediatric kidney transplant practice patterns and outcome benchmarks, 1987-2010: a report of the north American pediatric renal trials and collaborative studies. Pediatr Transplant 17:149–157CrossRefGoogle Scholar
  30. 30.
    Kaabak MM, Babenko NN, Shapiro R, Maschan AA, Zokoev AK, Schekaturov SV, Vyunkova JN, Dymova OV (2017) Eight-year follow-up in pediatric living donor kidney recipients receiving alemtuzumab induction. Pediatr Transplant.
  31. 31.
    Lerch C, Kanzelmeyer NK, Ahlenstiel-Grunow T, Froede K, Kreuzer M, Drube J, Verboom M, Pape L (2017) Belatacept after kidney transplantation in adolescents: a retrospective study. Transpl Int 30:494–501CrossRefGoogle Scholar
  32. 32.
    Ekberg H, Tedesco-Silva H, Demirbas A, Vitko S, Nashan B, Gurkan A, Margreiter R, Hugo C, Grinyo JM, Frei U, Vanrenterghem Y, Daloze P, Halloran PF, ELITE-Symphony Study (2007) Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 357:2562–2575CrossRefGoogle Scholar
  33. 33.
    Vincenti F, Rostaing L, Grinyo J, Rice K, Steinberg S, Gaite L, Moal MC, Mondragon-Ramirez GA, Kothari J, Polinsky MS, Meier-Kriesche HU, Munier S, Larsen CP (2016) Belatacept and long-term outcomes in kidney transplantation. N Engl J Med 374:333–343CrossRefGoogle Scholar
  34. 34.
    Hertig A, Zuckermann A (2015) Rabbit antithymocyte globulin induction and risk of post-transplant lymphoproliferative disease in adult and pediatric solid organ transplantation: an update. Transpl Immunol 32:179–187CrossRefGoogle Scholar
  35. 35.
    Stojanovic J, Adamusiak A, Kessaris N, Chandak P, Ahmed Z, Sebire NJ, Walsh G, Jones HE, Marks SD, Mamode N (2017) Immune desensitization allows pediatric blood group incompatible kidney transplantation. Transplantation 101:1242–1246CrossRefGoogle Scholar
  36. 36.
    Mamode N, Marks S (2016) Desensitization protocols for prospective pediatric renal transplant patients. Pediatr Nephrol 31:1549–1551CrossRefGoogle Scholar

Copyright information

© IPNA 2017

Authors and Affiliations

  1. 1.Department of Pediatric NephrologyHannover Medical SchoolHannoverGermany

Personalised recommendations